Synthetic approaches towards a radiofluorinated agent for imaging Alzheimer's disease

Permanent URL: http://hdl.handle.net/2047/d20128875
Title:
Synthetic approaches towards a radiofluorinated agent for imaging Alzheimer's disease
Creator:
Chang, Tracy (Author)
Contributor:
Hanson, Robert N. (Advisor)
Aggen, James (Committee member)
O'Doherty, George A. (Committee member)
Publisher:
Boston, Massachusetts : Northeastern University, 2015
Date Accepted:
April 2015
Date Awarded:
May 2015
Type of resource:
Text
Genre:
Masters theses
Format:
electronic
Digital origin:
born digital
Abstract/Description:
Alzheimer's Disease (AD) is a neurodegenerative disease in which the patient's memory slowly declines, accompanied by general physical degeneration and death. There are several hypotheses about the cause of AD, one of them being the aggregation of amyloid beta (Aβ) protein. Currently, the only way to definitively identify AD is by postmortem autopsy, in which the Aβ plaque is clearly identified. A potential noninvasive method for early diagnosis is a radiotracer for imaging Aβ deposits in the brain using positron emission tomography (PET) or single photon emission computer tomography (SPECT).

The Vasdev group has proposed alternative radio-fluorinated tracers that bind to Aβ plaque more effectively. In their initial studies, 8-hydroxyquinolines labeled with fluorine-18 at the 4- or 2- positions were evaluated for their potential clinical utility. Due to the synthetic inaccessibility of the 3- position, that analog was not pursued. As part of our ongoing collaboration with the Vasdev group, we undertook the preparation of the corresponding 3-fluoro and 3-iodo 8-hydroxyquinolines and their precursors.

Several synthetic strategies were devised and evaluated to obtain precursors and nonlabeled standards for in vitro/in vivo studies. Substantial prior art exists for aromatic radiofluorination precursors, including diaryl iodonium salts and aryl stannanes. During this project, many synthetic issues were encountered, which lead to the development of an alternative strategy proceeding via a stannylated intermediate that could be used for either radiofluorinated (PET) or radioiodinated (SPECT) tracers. The results of these synthetic studies are discussed, as well as the potential for applications for therapeutic areas.
Subjects and keywords:
Alzheimer's disease
Amyloid beta
nuclear medicine
positron emission tomography
Chemistry
Organic Chemistry
Radioactive tracers
Amyloid beta-protein precursor -- Synthesis
Amyloid beta-protein
Alzheimer's disease -- Imaging
Brain -- Imaging
Tomography, Emission
Nuclear medicine -- Data processing
DOI:
https://doi.org/10.17760/d20128875
Permanent URL:
http://hdl.handle.net/2047/d20128875
Use and reproduction:
In Copyright: This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the right-holder(s). (http://rightsstatements.org/vocab/InC/1.0/)
Copyright restrictions may apply.

Downloads